Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, China.
Acta Biomater. 2012 Feb;8(2):599-607. doi: 10.1016/j.actbio.2011.11.006. Epub 2011 Nov 11.
In this study, novel multifunctional ternary complexes of biotinylated transferrin-avidin-biotin-poly(ethylene glycol)-poly(L-glutamate acid)/poly(2-(2-aminoethylamino) ethyl methacrylate)/doxorubicin-poly(L-aspartic acid)/pDNA (TAB/PIC-D/pDNA complexes) were prepared based on polyion complex micelles (PIC) and the avidin-biotin system, which aimed to target co-delivery of anti-cancer doxorubicin and gene. Cytotoxicity studies revealed that PIC-D could have anti-tumor effect on HeLa cells and HepG2 cells; TAB coating could increase the biocompatibility of PIC-D/pDNA complexes and the targeting delivery efficiency of doxorubicin. TAB/PIC-D/pDNA complexes possessed higher transfection efficiency than the unmodified complexes in serum, and transferrin could enhance luciferase expression in HeLa cells and HepG2 cells. Furthermore, confocal laser scanning microscopy showed that doxorubicin and gene could be delivered into HepG2 cells simultaneously by TAB/PIC-D/pDNA complexes. The formation of the ternary complexes provides a facile approach to constructing a multifunctional delivery system for targeted co-delivery of anticancer drugs and gene.
在这项研究中，基于聚离子复合物胶束（PIC）和亲和素-生物素系统，制备了新型多功能三元复合物，即生物素化转铁蛋白-亲和素-生物素-聚（乙二醇）-聚（L-谷氨酸）/聚（2-（2-氨基乙基）氨基）乙基甲基丙烯酸酯/阿霉素-聚（L-天冬氨酸）/pDNA（TAB/PIC-D/pDNA 复合物），旨在靶向共递抗癌药物阿霉素和基因。细胞毒性研究表明，PIC-D 对 HeLa 细胞和 HepG2 细胞具有抗肿瘤作用；TAB 涂层可以提高 PIC-D/pDNA 复合物的生物相容性和阿霉素的靶向递送效率。TAB/PIC-D/pDNA 复合物在血清中的转染效率高于未修饰的复合物，转铁蛋白可以增强 HeLa 细胞和 HepG2 细胞中的荧光素酶表达。此外，共聚焦激光扫描显微镜显示，TAB/PIC-D/pDNA 复合物可以同时将阿霉素和基因递送到 HepG2 细胞中。三元复合物的形成提供了一种简便的方法来构建用于靶向共递抗癌药物和基因的多功能递送系统。
